Therapeutic Mechanisms of Bile Acids and Nor-Ursodeoxycholic Acid in Non-Alcoholic Fatty Liver Disease

2017 ◽  
Vol 35 (3) ◽  
pp. 282-287 ◽  
Author(s):  
Daniel Steinacher ◽  
Thierry Claudel ◽  
Michael Trauner

Non-alcoholic fatty liver disease is one of the most rapidly rising clinical problems in the 21st century. So far no effective drug treatment has been established to cure this disease. Bile acids (BAs) have a variety of signaling properties, which can be used therapeutically for modulating hepatic metabolism and inflammation. A side-chain shorted derivative of ursodeoxycholic acid (UDCA) is 24 nor-ursodeoxycholic acid (NorUDCA) and it represents a new class of drugs for treatment of liver diseases. NorUDCA has unique biochemical and therapeutic properties, since it is relatively resistant to conjugation with glycine or taurine compared to UDCA. NorUDCA undergoes cholehepatic shunting, resulting in ductular targeting, bicarbonate-rich hypercholeresis, and cholangiocyte protection. Furthermore, it showed anti-fibrotic, anti-inflammatory, and anti-lipotoxic properties in several animal models. As such, NorUDCA is a promising new approach in the treatment of cholestatic and metabolic liver diseases. This review is a summary of current BA-based therapeutic approaches in the treatment of the fatty liver disease.

2019 ◽  
Vol 63 (20) ◽  
pp. 1900487 ◽  
Author(s):  
Petar Dianov Petrov ◽  
Maria Victoria García‐Mediavilla ◽  
Carla Guzmán ◽  
David Porras ◽  
Esther Nistal ◽  
...  

Author(s):  
M. M. Dolzhenko ◽  
L. I. Konoplyanik

The clinical morphological manifestations of the course of non‑alcoholic fatty liver disease in patients, non‑alcohol drinkers, include steatohepatosis, non‑alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. There are four basic mechanisms in the pathogenesis of non‑alcoholic fatty liver disease: bile acid lipotoxicity, insulin resistance, systemic inflammation, increased oxidative stress and lipid peroxidation. Non‑alcoholic fatty liver disease increases the risk of onset, development and progression of the cardiovascular diseases independently from other predictors and manifestations of the metabolic syndrome. The complex treatment of patients with coronary heart disease, combined with the non‑alcoholic fatty liver disease includes diet, physical exercises, body mass reduction and drug therapy. The medications for this category of patients must be maximal safe and result in the improving of the clinical, laboratory and morphological parameters of liver. Ursodeoxycholic acid is one of the most effective medications with the mechanisms of action associated with the normalization of the hepatoenteric circulation of bile acids and a number of biologically active substances. It also possesses the cytoprotective and antiapoptotic action, affects the FXR­metabolic nuclear receptor, which plays an important role in the physiology of vascular pathology, is an important transcriptional regulator of bile acids, lipids and glucose metabolism. Ursodeoxycholic acid is able to suppress eosinophilic inflammation not only in the gastrointestinal tract. It improves histopathological changes in airway remodeling, that can be connected with the modulation of cytokines and inhibition of apoptosis of epithelial cells of the respiratory tract. Ursodeoxycholic acid can be potentially effective preparation for the reduction of fluid volume in pulmonary edema and prevention of lung damage caused by fat embolism syndrome. Moreover, its positive effects have been proved as regards the airway epithelial cells at cystic fibrosis. Taking into account that ursodeoxycholic acid inhibits pro‑inflammatory cytokines, has strong antioxidative properties and acts as a famous hepatoprotector, it can be effective in the treatment of coronavirus disease (COVID­19). In Ukraine Ursonost is available, it is one of the well‑known preparations containing ursodeoxycholic acid and advantageously distinguished by high quality and ease of dosing. It is bioequivalent to the reference drug due to the highest quality of the substance and modern production technology. The large evidence base on ursodeoxycholic acid allows the drug Ursonost to be considered as a drug with pronounced multipotent properties, thus it is indicated for the treatment of patients with non‑alcoholic and alcoholic fatty liver disease, especially in combination with the coronary heart disease, of conditions, associated with bile reflux (duodenogastric, duodenogastroesophageal reflux), biliary sludge, primary biliary cirrhosis, gallstone disease (for dissolving X‑ray negative stones) and other metabolic disorders. Ursonost preparation is available as 150 and 300 mg capsules, that facilitates the drug dosing depending on the body mass of a patient and a clinical situation.


2013 ◽  
Vol 58 (1) ◽  
pp. 119-125 ◽  
Author(s):  
Rui E. Castro ◽  
Duarte M.S. Ferreira ◽  
Marta B. Afonso ◽  
Pedro M. Borralho ◽  
Mariana V. Machado ◽  
...  

2016 ◽  
Vol 23 (4) ◽  
pp. 2016420
Author(s):  
Nataliya Karpyshyn

Non-alcoholic fatty liver disease is considered as an independent predictor of cardiovascular diseases which plays an important role in the development of ischemic heart disease. The drug most frequently used for treating this comorbidity is atorvastatin which favours better survival outcomes and is essential in the primary and secondary prevention of cardiovascular diseases. Ursodeoxycholic acid is prescribed as an alternative therapy for ischemic heart disease with co-existent non-alcoholic fatty liver disease and obesity to eliminate statin side effects. The use of ursodeoxycholic acid as a hepatoprotector in comprehensive basic treatment contributes to the improvement of the cardiovascular system in patients with ischemic heart disease as well as the increase in treatment efficacy; it improves the functional status of the liver affecting the major pathogenic mechanisms of the disease.The objective of the research was to study the effect of combined hypolipidemic therapy with atorvastatin and ursodeoxycholic acid on the indices of blood lipids, liver transaminase levels, functional status of the liver and the course of non-alcoholic fatty liver disease in patients with ischemic heart disease and obesity.Materials and methods. 20 patients with ischemic heart disease, co-existent non-alcoholic fatty liver disease and obesity were examined. They received ursodeoxycholic acid in addition to atorvastatin for four weeks. All the patients underwent clinical tests, visceral ultrasonography, blood lipid test, liver transaminase test and 13C-methacetin breath test.Results. The study revealed a significant decrease in the level of the pro-atherogenic fractions of blood lipids (р<0.01) as well as an improved functional status of the liver due to a significant increase in metabolic capacity of the liver and cumulative dose on the 40th and 120th minutes after ursodeoxycholic acid administration (р<0.01).Conclusions. The use of ursodeoxycholic acid in addition to atorvastatin in patients with ischemic heart disease, co-existent non-alcoholic fatty liver disease and obesity makes it possible to avoid the adverse effect of hypolipidemic therapy on the functional status of the liver.


Author(s):  
Nina Vodošek Hojs ◽  
Aftab Ala ◽  
Debasish Banerjee

Cardiovascular disease in patients with liver disease, previously uncommon, is rising because of an increasing incidence of non-alcoholic fatty liver disease and better survival of patients with viral hepatitis, particularly hepatitis C. Liver dysfunction alters the pharmacokinetics and pharmacodynamics of many drugs, and hence careful use and dose adjustments are necessary. This chapter describes common cardiovascular conditions and the pharmacotherapy in patients with different liver diseases.


1970 ◽  
Vol 1 (2) ◽  
pp. 60-63
Author(s):  
Ankush Mittal ◽  
Brijesh Sathian ◽  
Nishida Chandrasekharan ◽  
Akshay Lekhi ◽  
Shamim Mohammad Farooqui ◽  
...  

Background: Liver diseases is apparently increasing and emerging as a major public health problem. Worldwide,  chronic hepatitis B has  become  the tenth leading cause of death  and  persons infected with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV), are about 350 million and  125 million respectively. The aim of current retrospective comparative study was concerned primarily to evaluate the significance of non invasive serological markers for diagnosing liver diseases and their predictive implications in Pokhara valley. Materials and Methods: It was a hospital based retrospective study carried out using the data maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st June 2009 and 31st   October 2010.  The variables collected were total protein, albumin, AST, ALT, total bilirubin, direct bilirubin.  Descriptive statistics and testing of hypothesis were used for the analysis. Data was analyzed using EPI INFO and SPSS 16 software. Results: Of 515 subjects, 120 were suffering from viral hepatitis and 88 had non alcoholic fatty liver disease. In cases of viral hepatitis, mean values of AST (CI 730.65 to 902.68) and ALT (CI 648.14 to 847.59) were markedly increased as compared to controls. Mild to moderate elevations in serum levels of aspartate aminotransferase (CI 43.42 to 49.49), alanine aminotransferase (CI 43.90 to 53.92) were the most common laboratory abnormalities found in patients with nonalcoholic fatty liver disease. Conclusion: Non invasive tests have demonstrated a reasonable ability to identify significant fibrosis, cirrhosis in particular, nor is it surprising that liver disease specialists and patients favour a non invasive approach.Key words: Viral hepatitis; Nonalcoholic fatty liver disease; Nepal.DOI: http://dx.doi.org/10.3126/nje.v1i2.5137 Nepal Journal of Epidemiology 2011;1 (2):60-63


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